Chapter 19: Electrophilic Addition to Alkenes

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Okay, let's really get into this.

Have you ever looked at a chemical reaction?

I mean, really looked and wondered not just what is happening, but why?

Like, why that way?

Today we're doing a deep dive into chapter 19 of Clayton, Greaves, and Warren's Organic Chemistry.

It's all about electrophilic addition to alkenes.

And this isn't just, you know, memorizing reactions.

It's about getting the logic, the flow of electrons.

Exactly.

It's foundational stuff.

Understanding why these reactions happen gives you predictive power.

So our mission, if you will, for this deep dive is to unpack the core ideas.

We're focusing on the mechanisms that electron dance, how functional groups change, the whole 3D picture with stereochemistry,

and even how it fits into planning synthesis, you know, retrosynthesis, like a blueprint for making molecules.

Yeah, and it's fascinating because this chapter builds so much on what comes before,

like, carbocation stability, SN1, SN2 ideas.

And understanding this addition process helps you predict outcomes, plan how to build molecules, and even understand some biological stuff, like how certain toxins form harmful epoxides in the body.

Right, like those aflatoxins you mentioned,

nasty stuff.

It really shows how you can take a simple double bond, that CCC, and turn it into all sorts of other things.

It's incredibly versatile.

Okay, so the plan is, start with bromine addition, the classic, then epoxides.

Useful little rings.

Then the tricky parts, like unsymmetrical alkenes, where does everything go?

That's regioselectivity.

And dilanes, they behave a bit differently.

And controlling the 3D shape, stereospecificity.

Then dihydroxylation, breaking CB bonds completely.

Olsenolysis, yeah.

Finally, different ways to add water.

Sounds good.

Sounds like a plan.

Let's go.

All right, basics first.

Alkenes as nucleophiles.

That pi bond, right, it's like this cloud of electrons sticking out.

Mmm, electron rich, ready to donate.

And the electrophile, like bromine Br2, it wants electrons, it's got somewhere for them to go, an empty orbital, essentially.

Exactly.

Even though Br2 is nonpolar overall,

as it approaches the alkenes electron cloud, it gets polarized.

One bromine becomes slightly positive, ready to accept those pi electrons.

And the really cool part is what happens next.

It doesn't just form a carbocation initially.

The bromine atom uses its lone pairs to form a three -membered ring, the bromonium ion.

Ah, right, the bridge.

Not just the theory you said?

No, not at all.

We've got solid evidence -like x -ray structures of stable hindered versions of these ions.

It definitely exists.

And this intermediate is key because it blocks one face of the original double bond.

So the bromide ion, Br, which was kicked off, has to attack from the back.

Like an SN2 attack.

Pretty much, yeah, an SN2 -like attack on one of the carbons in the ring.

This forces an inversion of configuration there.

So you get anti -edition overall.

The two bromines end up on opposite faces.

Precisely.

It dictates the stereochemistry.

And that's why alkenes decolorize bromine water.

That orange -brown color just vanishes.

It's not magic, it's chemistry.

It's the direct consequence of that mechanism, yeah.

Very visual confirmation.

Okay, so from bromine, let's talk about oxygen.

Can we make similar three -membered rings with oxygen?

Epoxides?

Absolutely.

Epoxides are, you could say, the oxygen cousins of bromonium ions.

But they're generally much more stable and incredibly useful in synthesis.

They're like spring -loaded functional groups.

How do we make them reliably from alkenes?

The go -to method is using a peroxy acid, often called a peracid.

Something like MCPBA is really common.

MCPBA.

Metachloroperoxybenzoic acid.

The alkenes pi electrons attack the weak oxygen bond in the peracid.

Specifically, the oxygen atom further from the carbonyl group acts as the

happens in one concerted step.

Concerted, meaning all bondmaking and breaking happens at the same time.

Essentially, yes.

The alkene attacks the oxygen, the alkene bond breaks, a proton gets transferred.

It's quite elegant.

And it's an oxidation of the alkenes.

And the stereochemistry.

Does it keep the original alkene geometry?

It does.

That's crucial.

It's stereospecific.

If you start with a cis alkene, you get a cis epoxide.

Start with trans, you get trans.

Wow.

So the geometry is locked in during the reaction.

Exactly.

The oxygen adds to one phase of the double bond and the original substituent is stay put relative to each other.

What about reaction speed?

Do all alkenes react the same?

Good question.

No, they don't.

More substituted alkenes react faster.

Those alkyl groups push electron density into the double bond.

Making it more nucleophilic.

Precisely.

They raise the energy of the highest occupied molecular orbital.

More energetic electrons are more reactive.

So you could potentially react one double bond in a molecule but leave another one alone.

Yes.

If there's enough difference in substitution, we see that with cyclopentadine under the right conditions, you can get just the mono epoxide selectively reacting one of the double bonds.

Buffering is often important there to prevent the epoxide from opening up under acidic conditions.

And this isn't just neat lab chemistry.

You mentioned biological relevance, like with those carcinogenic epoxides.

Right.

Things like aflatoxins get metabolized in the liver, sometimes forming highly reactive epoxides via enzymes.

These epoxides can then react with the DNA, causing mutations.

Understanding how epoxides form and react is vital.

And reagents like dimepaldeoxirane, DMDO you mentioned?

Yes, DMDO.

That's another way to make epoxides, often used for ones that might be sensitive to conditions of peroxide epoxidation.

So quite a clean oxidant.

Is there another way to make epoxides, maybe linking back to bromine?

There is actually.

If you do the bromination reaction in water instead of, say, dichloromethane, you form a bromohydrin, a bromine on one carbon, and OH on the adjacent one.

Then if you treat that bromohydrin with a base, the base deprotonates the OH group to make an alkoxide.

Right.

O minus.

And that O minus can then swing around and do an intermolecular SN2 reaction, attacking the carbon with the bromine and kicking out the bromide ions.

Snapping the ring shut.

Exactly.

Forms epoxide that way, too.

It's a neat two -step sequence.

Shows how reactions connect.

Okay.

Let's shift gears a bit.

We've mostly talked about symmetrical situations, like adding Br2 or making an epoxide.

What happens if you add something unsymmetrical, like HBr, to an unsymmetrical alkene, like propene, maybe?

Ah, now we get into regioselectivity.

Where do the H and the Br go?

Unlike bromine, hydrogen can't form a bridged intermediate.

So no hydrogenonium ion?

Nope.

When the alkene pi bond attacks the H plus from HBr, it forms a regularly carbocation intermediate.

Okay, a positive charge on a carbon.

And the key principle here is carbocation stability.

The reaction will proceed through the most stable possible carbocation.

And more substituted carbocations are more stable, right?

Tertiary better than secondary, better than primary.

Exactly.

So if you add H plus to propene, you could form a primary carbocation or a secondary one.

The secondary is much more stable, so that's the one that forms preferentially.

And then the bromide ion, Br, attacks that secondary carbocation.

The bromine ends up on the more substituted carbon, and the hydrogen goes to the less substituted one.

That sounds like Markovnikov's rule.

It is Markovnikov's rule.

But the rule is just an observation.

The reason is carbocation stability.

Understanding the why is much more powerful than just memorizing the rule.

Think about styrene adding H plus gives a benzylication, super stable due to resonance.

The Br ends up there.

Got it.

Stability rules.

What about dynes?

Molecules with two double bonds?

Dynes, especially conjugated dynes where the double bonds are separated by one single bond, are even more nucleophilic than simple algaes.

Their HOMO energy is higher.

So they react faster.

Often, yes.

And protonating a conjugated dyne, like isoprene or butythene, gives you an allylicication.

That positive charge is delocalized over multiple atoms through resonance.

Very stable.

And does that affect where the bromide adds?

It does.

And it can get complicated.

With dutidine, for instance, the bromide can attack at C2, giving the 1 ,2 addition product, or at C4, giving the 1 ,4 addition product.

My two different products.

Ah, this is classic kinetic versus thermodynamic control.

At low temperatures, the reaction is faster to form the Proof Q product, kinetic control, because the bromide attacks the carbon closest to where the proton added, which might bear more of the positive charge initially.

Okay, fastest route wins.

But at higher temperatures, the reactions become reversible.

The less stable 1 ,1 ,2 product can revert back to the allylication, and eventually the more stable 1 ,1 ,4 product accumulates, because it's thermodynamically favored.

Thermodynamic control.

So temperature is like a switch between the fast product and the stable product.

Exactly.

It's a beautiful example of reaction dynamics.

Going back to bromine addition, but with unsymmetrical alkenes, you mentioned something about a loose SN2.

What's that about?

If you add Br2 in, say, methanol.

Right.

So you still form an unsymmetrical bromonium ion.

Now, when the nucleophile attacks maybe methanol, the solvent, where does it go?

You might expect SN2 attack at the less hindered curve.

Yeah, that makes sense sterically.

But often, it attacks the more substituted carbon.

It's not quite SN1, because the full carbocation doesn't form.

And it's not quite a classic SN2 on a neutral substrate.

Think of it as the CBR bond starts to break before the nucleophile fully attacks.

A partial positive charge builds up, and it builds up more on the carbon that can handle it better, the more substituted one.

So the nucleophile is drawn there.

It's somewhere between SN1 and SN2.

A loose transition state.

So the electronics, the stability kind of win out over sterics in that case.

Often, yes.

It highlights that mechanisms are sometimes a spectrum, not just distinct categories.

And does this apply to opening epoxides too?

It does, and it's crucial.

How an epoxide opens depends entirely on the conditions, acidic or basic.

Okay, how so?

Under acid catalysis, you protonate the epoxide oxygen first.

This makes the CO bonds weaker and easier to break.

The nucleophile, often weak like water or an alcohol, attacks the carbon that can better stabilize the developing positive charge as the CO bond breaks.

So the more substituted carbon again, like the bromonium ion case.

Exactly.

Similar logic.

Attack at the more substituted carbon, leading to Markovnikov -type regioselectivity.

But under basic conditions?

Under basic conditions, you typically use a strong nucleophile, like an alkoxide or Grignard region.

There's no protonation first.

The strong nucleophile performs a direct SN2 attack.

And SN2 is sensitive to steric hindrance.

Precisely.

So under basic conditions, the nucleophile attacks the less substituted carbon of the epoxide.

It's the anti -Markovnikov outcome.

Wow, so just by choosing acid or base, you completely control where the nucleophile ends up.

That's the power of understanding mechanism.

You dictate the outcome by choosing the right conditions.

Incredible control.

Okay, moving beyond just adding one group, what about adding two hydroxyl groups?

Dihydroxylation.

Another really useful transformation.

Yeah.

Making one very two dials.

And again, we have stereochemical control.

Two main ways to do it, giving opposite stereochemistry.

Anti and syn.

You got it.

For anti -dihydroxylation OH groups on opposite faces, you can use the epoxide route we just discussed.

Make the epoxide first.

Using MCPBA maybe?

Yep.

And then open it with water under acidic conditions.

Since the opening is SN2 -like with backside attack by water, you get inversion, leading to the overall anti -addition of the two OH groups relative to the original alkene plane.

Okay, epoxide, then acid catalyzed water opening gives anti.

How do you get syn both OHs on the same face?

For syn -dihydroxylation, the classic region is osmium tetroxide O5 -4.

Sounds expensive and toxic.

It is, but you can use it catalytically, which helps a lot.

You need a co -oxidant like NMO and methylmorpholine and oxide to regenerate the OH4 after it reacts.

The mechanism is neat.

The OH4 adds across the double bond in a concerted cyclic process, a paracyclic reaction forming a cyclic osmate ester.

Both oxygens add to the same face of the alkene at the same time.

So that locks in the syn geometry right there.

Exactly.

Then you cleave the osmate ester, usually reductively, to release the syn -diol.

Two methods, opposite stereochemical outcomes.

Very cool.

Now what about breaking the double bond entirely?

Cleavage reactions.

Sometimes you want to chop that cc bond right in half.

Two main ways again.

Period 8 cleavage of diols and ozonolysis.

Okay, period 8 first.

Does that link to the dihydroxylation?

It often follows syn -dihydroxylation.

If you have a two -dial sodium period 8,

NiO4 will selectively cleave the cc bond between the two hydroxyl groups.

And what do you do?

You get two carbonyl compounds.

If the carbons had hydrogens, you get aldehydes.

If they were fully substituted, you get ketones.

It's a way to break down a molecule and see what pieces it was made of or to synthesize specific carbonyls.

And ozonolysis.

Ozone.

Ozonolysis does the cleavage directly on the alkene.

Ozone adds across the double bond to form an initial melosinide, which quickly rearranges to a more stable ozonide.

Still pretty unstable stuff.

Okay, then what?

Then comes a workup, and this is where you have choices.

You need to break down the ozonide.

A reductive workup, maybe using zinc and acetic acid or domethyl sulfide, DMS,

cleaves the ozonide to give aldehydes or ketones.

It stops the oxidation there.

And if you want carboxylic acids?

Then you use an oxidative workup, often with hydrogen peroxide.

This cleaves the ozonide and oxidizes any aldehyde fragments all the way up to carboxylic acids.

Ketones stay as ketones.

So again, control based on the workup conditions.

Aldehyde ketones or carboxylic acid ketones.

Precisely.

Very powerful for synthesis.

All right, last big topic, adding water.

Hydration.

We know simple acid and water isn't always great because of provocation rearrangements.

Right.

It works okay if you form a nice stabilization, and rearrangements aren't an issue, but often you want more reliable methods.

Like oxymercuration demercuration.

That's the reliable Markovnikov hydration.

You use mercury acetate and water, which adds across the double bond via a bridged macuridium ion, intermediate similar to the bromonium ion.

Uh -huh.

So that prevents rearrangements.

Exactly.

Water then attacks the more substituted carbon of that bridged ion.

Then in a second step, you use sodium borohydride, maybe H4, to replace the mercury with a hydrogen.

Net result.

Markovnikov addition of H and OH, reliably.

Clean Markovnikov hydration.

But what if we want the opposite?

Anti -Markovnikov hydration.

OH on the less substituted carbon.

For that we need a completely different approach.

Hydroboration oxidation.

Boron chemistry.

Yep.

You use borane, BH3, often complex with something like THF to stabilize it.

Borane adds across the double bond.

Now boron is less electronegative than hydrogen, so electronically the hydrogen acts like the positive part and adds to the more substituted carbon, while the boron, BH2 group, adds to the less substituted carbon.

Sterics probably help too.

Boron group is bigger than H.

Sterics definitely play a role too.

Guiding the bulky boron group to the less crowded spot so you get anti -Markovnikov addition of H and BH3.

And then how do you get the OH group?

Second step.

Yeah.

Oxidation.

You treat the organoborane intermediate with hydrogen peroxide and aqueous base like NaOH.

This magically replaces the carbon -boron bond with a carbon -oxygen bond with pretension of configuration.

So the OH group ends up exactly where the boron was on the less substituted carbon.

Exactly.

Net result.

Anti -Markovnikov addition of water.

Beautiful control over regiochemistry.

Wow.

Okay.

So summing up chapter 19,

it's really about understanding how that electron -rich pi bond reacts with electrophiles.

We've seen bromine addition via bromonium ions giving anti -products, epoxide formation being stereospecific, and how they're opening depends on acid or base catalysis.

Carbication stability driving Markovnikov regioselectivity, but also kinetic versus thermodynamic control in the motion lines.

Right.

And then the specific methods for dihydroxylation, syn with ozophore, anti -via epoxides, cleavage with ozone, or periodate.

And finally, controlled hydration Markovnikov via oxymercuration,

anti -Markovnikov via hydroboration.

It's a whole toolkit built around that double bond, all governed by mechanistic principles.

Understanding why the intermediates, the electron flow, lets you predict and control the outcome.

It really does.

And it leads to a final thought perhaps.

If we understand these subtle electron movements so well, how does that deep knowledge allow us to design reactions to build even more complex molecules?

Molecules may be needed for medicine or materials, things nature hasn't even thought of yet.

It's moving beyond just explaining reactions to actively designing molecular future.

A powerful thought.

It really highlights the creativity in organic chemistry.

Well, thank you for joining us on this deep dive into electrophilic additions.

We hope exploring chapter 19 with us has made these reactions feel a bit more intuitive and powerful.

Hope it was helpful.

And thank you as always for being part of the Last Minute Lecture family.